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INTRODUCTION: Therapeutic offloading devices, including insoles, shoes, and other orthoses, are some of the most commonly used interventions to treat or prevent diabetic foot ulceration. Custom-made offloading devices are increasingly used to offset the development of foot ulcers. However, whether these devices are more effective than prefabricated standard offloading devices is uncertain. Therefore, this systematic review collates and examines evidence on the efficacy of custom-made offloading devices in preventing foot ulcer incidence and recurrence in people diagnosed with diabetes. METHODS: Five scientific databases were searched, covering 2011-2023. Initial searches and screening were carried out independently by two researchers. Studies meeting the inclusion criteria were further examined through additional screenings, and critical appraisal. Data relevant to the review aims were extracted and analysed within a narrative synthesis. RESULTS: Of the 1,715 articles found in the initial searches, nine papers were found to meet inclusion criteria and were included in the review. The evidence shows that custom-made offloading devices are likely to be more effective for reducing or preventing diabetic foot ulcers than standard offloading devices. However, due to a lack of data it remains uncertain whether custom-made offloading devices are more cost-effective for preventing ulceration compared to standard insoles. Likewise, due to measurement heterogeneity between studies and lack of data, it is unclear whether adherence is higher in users of custom-made offloading devices, and whether such devices deliver significantly greater reductions in peak pressure as compared to standard offloading devices. CONCLUSION: Custom-made offloading devices are more effective than standard devices for preventing diabetic foot ulceration, and we recommended their use when feasible; however, there remains uncertainty regarding their cost-effectiveness compared to standard insoles and offloading devices.
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BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Piridinas , Humanos , Persona de Mediana Edad , Femenino , Masculino , Terapia Neoadyuvante/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto Joven , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , AdolescenteRESUMEN
Backgrounds: As a conserved signaling pathway, mitogen-activated protein kinase (MAPK) cascade regulates cellular signaling in response to abiotic stress. High temperature may contribute to a significant decrease in economic yield. However, research into the expression patterns of StMAPKK family genes under high temperature is limited and lacks experimental validation regarding their role in supporting potato plant growth. Methods: To trigger heat stress responses, potato plants were grown at 35°C. qRT-PCR was conducted to analyze the expression pattern of StMAPKK family genes in potato plants. Plant with StMAPKK5 loss-of-function and gain-of-function were developed. Potato growth and morphological features were assessed through measures of plant height, dry weight, and fresh weight. The antioxidant ability of StMAPKK5 was indicated by antioxidant enzyme activity and H2O2 content. Cell membrane integrity and permeability were suggested by relative electrical conductivity (REC), and contents of MDA and proline. Photosynthetic capacity was next determined. Further, mRNA expression of heat stress-responsive genes and antioxidant enzyme genes was examined. Results: In reaction to heat stress, the expression profiles of StMAPKK family genes were changed. The StMAPKK5 protein is located to the nucleus, cytoplasm and cytomembrane, playing a role in controlling the height and weight of potato plants under heat stress conditions. StMAPKK5 over-expression promoted photosynthesis and maintained cell membrane integrity, while inhibited transpiration and stomatal conductance under heat stress. Overexpression of StMAPKK5 triggered biochemical defenses in potato plant against heat stress, modulating the levels of H2O2, MDA and proline, as well as the antioxidant activities of CAT, SOD and POD. Overexpression of StMAPKK5 elicited genetic responses in potato plants to heat stress, affecting heat stress-responsive genes and genes encoding antioxidant enzymes. Conclusion: StMAPKK5 can improve the resilience of potato plants to heat stress-induced damage, offering a promising approach for engineering potatoes with enhanced adaptability to challenging heat stress conditions.
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Classification-based myoelectric control has attracted significant interest in recent years, leading to prosthetic hands with advanced functionality, such as multi-grip hands. Thus far, high classification accuracies have been achieved by increasing the number of surface electromyography (sEMG) electrodes or adding other sensing mechanisms. While many prescribed myoelectric hands still adopt two-electrode sEMG systems, detailed studies on signal processing and classification performance are still lacking. In this study, nine able-bodied participants were recruited to perform six typical hand actions, from which sEMG signals from two electrodes were acquired using a Delsys Trigno Research+ acquisition system. Signal processing and machine learning algorithms, specifically, linear discriminant analysis (LDA), k-nearest neighbors (KNN), and support vector machines (SVM), were used to study classification accuracies. Overall classification accuracy of 93 ± 2%, action-specific accuracy of 97 ± 2%, and F1-score of 87 ± 7% were achieved, which are comparable with those reported from multi-electrode systems. The highest accuracies were achieved using SVM algorithm compared to LDA and KNN algorithms. A logarithmic relationship between classification accuracy and number of features was revealed, which plateaued at five features. These comprehensive findings may potentially contribute to signal processing and machine learning strategies for commonly prescribed myoelectric hand systems with two sEMG electrodes to further improve functionality.
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Algoritmos , Electrodos , Electromiografía , Mano , Aprendizaje Automático , Procesamiento de Señales Asistido por Computador , Máquina de Vectores de Soporte , Humanos , Electromiografía/métodos , Mano/fisiología , Masculino , Adulto , Femenino , Análisis Discriminante , Adulto JovenRESUMEN
BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.
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Neoplasias Colorrectales , Neoplasias del Recto , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN , Inmunoterapia , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Neoplasias del Recto/genética , Neoplasias del Recto/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. METHODS: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. RESULTS: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. CONCLUSIONS: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.
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Neoplasias Encefálicas , Neoplasias del Colon , Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Síndromes Neoplásicos Hereditarios , Humanos , Estudios Retrospectivos , Oxaliplatino/uso terapéutico , Estadificación de Neoplasias , Antígeno Carcinoembrionario , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/cirugía , Pronóstico , Quimioterapia AdyuvanteRESUMEN
Radiotherapy (RT) is one of the important treatment modalities for non-small cell lung cancer (NSCLC). However, the maximum radiation dose that NSCLC patient can receive varies little. Therefore, the exploitation of novel RT sensitization approaches is a critical need for the clinical treatment. RT resistance in NSCLC is linked to tumor microenvironment (TME) hypoxia, cell cycle arrest and associated genetic alterations. Here, we designed a novel method for targeted delivery of quercetin (QT) and CeO2 to enhance RT sensitivity. We loaded QT into CeO2@ZIF-8-HA nanoparticles to prevent its degradation in the circulatory system and successfully delivered QT and CeO2 targeted to NSCLC tumors. Under the protection and targeted delivery of Zeolitic Imidazolate Framework-8 (ZIF-8), the nanocomplexes exhibited excellent catalytic mimetic activity in decomposing H2O2 into O2, thus significantly reversing the hypoxia of TME, while the radiosensitizer QT caused DNA damage directly after RT. In a subcutaneous tumor model, CeO2@ZIF-8-HA overcame radiation resistance and enhanced therapeutic efficacy. This multiple sensitization strategy combining delivery of QT and CeO2@ZIF-8-HA nanozymes opens a promising approach for RT of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Peróxido de Hidrógeno , Hipoxia Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Daño del ADN , Hipoxia/tratamiento farmacológico , Quercetina , Microambiente TumoralRESUMEN
This study focuses on novel design and evaluation of Elastic 50A (EL50) mechanical metamaterials with open-cell patterns for its potential application to lower limb residuum/socket interfaces, specifically that of a transtibial (TT) amputee. Mechanical characteristics, that is, effective Young's modulus (E), was tuned by altering metamaterial porosity, which was experimentally verified. Specifically, pore radius of the unit cell was varied to achieve a range of E-values (0.05-1.71 MPa) for these 3D printed metamaterials. Finite Element Analysis (FEA) was conducted to evaluate pressure distribution across key load-bearing anatomical sites of a TT residuum. Using designed metamaterials for homogeneous liners, pressure profiles were studied and compared with a silicone liner case. Additionally, a custom metamaterial liner was designed by assigning appropriate metamaterials to four load-sensitive and tolerant anatomical sites of the TT residuum. The results suggest that lowest pressure variation (PV), as a measure of pressure distribution levels and potential comfort for amputees, was achieved by the custom metamaterial liner compared to any of the homogeneous liners included in this study. It is envisaged that this work may aid future design and development of custom liners using now commonly available 3D printing technologies and available elastomer materials to maximise comfort, tissue safety and overall rehabilitation outcomes for lower limb amputees.
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Amputados , Miembros Artificiales , Humanos , Amputados/rehabilitación , Diseño de Prótesis , Resultado del Tratamiento , SiliconasRESUMEN
Employing a large sample of Chinese firms, this study examined the influence of corporate green innovation on firms' access to trade credit. The results indicated a positive association between green innovation and firms' capability to access trade credit, suggesting that suppliers value firms' green innovation capabilities. This relationship was strengthened after the implementation of the new Environmental Protection Law (EPL) in 2015, which enhanced the value of green innovation. The findings remained robust to several robustness tests. The results suggest that green innovation helps firms access trade credit through better environmental, social, and governance (ESG) scores and more state subsidy channels and plays a more pronounced role for financially constrained firms, non-state-owned enterprises, firms with lower bargaining power, and firms located in regions with better intellectual property rights protections. Green innovation is valuable for future corporate growth and shareholder value. Overall, this study reveals the value of green innovation through informal corporate financing.
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Innovación Organizacional , ChinaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies, and early detection plays a crucial role in enhancing curative outcomes. While colonoscopy is considered the gold standard for CRC diagnosis, noninvasive screening methods of DNA methylation biomarkers can improve the early detection of CRC and precancerous lesions. METHODS: Bioinformatics and machine learning methods were used to evaluate CRC-related genes within the TCGA database. By identifying the overlapped genes, potential biomarkers were selected for further validation. Methylation-specific PCR (MSP) was utilized to identify the associated genes as biomarkers. Subsequently, a real-time PCR assay for detecting the presence of neoplasia or cancer of the colon or rectum was established. This screening approach involved the recruitment of 978 participants from five cohorts. RESULTS: The genes with the highest specificity and sensitivity were Septin9, AXL4, and SDC2. A total of 940 participants were involved in the establishment of the final PCR system and the subsequent performance evaluation test. A multiplex TaqMan real-time PCR system has been illustrated to greatly enhance the ability to detect precancerous lesions and achieved an accuracy of 87.8% (95% CI 82.9-91.5), a sensitivity of 82.7% (95% CI 71.8-90.1), and a specificity of 90.1% (95% CI 84.3-93.9). Moreover, the detection rate of precancerous lesions of this assay reached 55.0% (95% CI 38.7-70.4). CONCLUSION: The combined detection of the methylation status of SEPT9, SDC2, and ALX4 in plasma holds the potential to further enhance the sensitivity of CRC detection.
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Neoplasias Colorrectales , Lesiones Precancerosas , Humanos , Metilación de ADN , Biomarcadores de Tumor/genética , Sensibilidad y Especificidad , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Detección Precoz del Cáncer/métodos , Proteínas del Citoesqueleto/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genéticaRESUMEN
BACKGROUND: Cognitive impairment is commonly seen after acute ischemic stroke (AIS). Sedentary behaviors increase the risk of dementia among community dwelling population. OBJECTIVE: This study aims to investigate the association of sedentary behaviors with poststroke cognitive impairment among older adults with minor AIS. METHODS: This cohort study recruited 594 older subjects with minor AIS from three hospitals in China during February 1, 2016, and December 31, 2018. Participants were followed up for two years and the sedentary time per day was self-reported at the end of follow-up. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). Participants were categorized into the high and low sedentary time group according to the median sedentary time of the participants. RESULTS: At two years of follow-up, the long sedentary time group had significantly lower MMSE scores than the short sedentary time group [median, (IQR): 21 (18 to 25) versus 22 (18 to 25), pâ=â0.368]. The long sedentary time group had a higher speed of cognitive decline than the short sedentary time group. Excessive sedentary time was associated with a higher risk of longitudinal cognitive decline (OR: 2.267, 95% CI: 1.594 to 3.225), adjusting for age, sex, education, body mass index, APOE genotype, comorbidities, symptoms of depression, anxiety, and insomnia, baseline MMSE scores and National Institute of Health Stroke Scale scores, cognitive therapy, and TOAST ischemic stroke subtypes. CONCLUSIONS: This study identified a possible link between sedentary behaviors and longitudinal cognitive decline among older patients with minor AIS, suggesting that reducing sedentary time might be helpful for preventing poststroke dementia.
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Disfunción Cognitiva , Demencia , Accidente Cerebrovascular Isquémico , Humanos , Anciano , Conducta Sedentaria , Estudios de Cohortes , Disfunción Cognitiva/epidemiologíaRESUMEN
BACKGROUND: Accurate prediction of response to neoadjuvant chemoradiotherapy is critical for subsequent treatment decisions for patients with locally advanced rectal cancer. OBJECTIVE: To develop and validate a deep learning model based on the comparison of paired MRI before and after neoadjuvant chemoradiotherapy to predict pathological complete response. DESIGN: By capturing the changes from MRI before and after neoadjuvant chemoradiotherapy in 638 patients, we trained a multitask deep learning model for response prediction (DeepRP-RC) that also allowed simultaneous segmentation. Its performance was independently tested in an internal and 3 external validation sets, and its prognostic value was also evaluated. SETTINGS: Multicenter study. PATIENTS: We retrospectively enrolled 1201 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy before total mesorectal excision. Patients had been treated at 1 of 4 hospitals in China between January 2013 and December 2020. MAIN OUTCOME MEASURES: The main outcome was the accuracy of predicting pathological complete response, measured as the area under receiver operating curve for the training and validation data sets. RESULTS: DeepRP-RC achieved high performance in predicting pathological complete response after neoadjuvant chemoradiotherapy, with area under the curve values of 0.969 (0.942-0.996), 0.946 (0.915-0.977), 0.943 (0.888-0.998), and 0.919 (0.840-0.997) for the internal and 3 external validation sets, respectively. DeepRP-RC performed similarly well in the subgroups defined by receipt of radiotherapy, tumor location, T/N stages before and after neoadjuvant chemoradiotherapy, and age. Compared with experienced radiologists, the model showed substantially higher performance in pathological complete response prediction. The model was also highly accurate in identifying the patients with poor response. Furthermore, the model was significantly associated with disease-free survival independent of clinicopathological variables. LIMITATIONS: This study was limited by its retrospective design and absence of multiethnic data. CONCLUSIONS: DeepRP-RC could be an accurate preoperative tool for pathological complete response prediction in rectal cancer after neoadjuvant chemoradiotherapy. UN SISTEMA DE IA BASADO EN RESONANCIA MAGNTICA LONGITUDINAL PARA PREDECIR LA RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE EN EL CNCER DE RECTO UN ESTUDIO DE VALIDACIN MULTICNTRICO: ANTECEDENTES:La predicción precisa de la respuesta a la quimiorradioterapia neoadyuvante es fundamental para las decisiones de tratamiento posteriores para los pacientes con cáncer de recto localmente avanzado.OBJETIVO:Desarrollar y validar un modelo de aprendizaje profundo basado en la comparación de resonancias magnéticas pareadas antes y después de la quimiorradioterapia neoadyuvante para predecir la respuesta patológica completa.DISEÑO:Al capturar los cambios de las imágenes de resonancia magnética antes y después de la quimiorradioterapia neoadyuvante en 638 pacientes, entrenamos un modelo de aprendizaje profundo multitarea para la predicción de respuesta (DeepRP-RC) que también permitió la segmentación simultánea. Su rendimiento se probó de forma independiente en un conjunto de validación interna y tres externas, y también se evaluó su valor pronóstico.ESCENARIO:Estudio multicéntrico.PACIENTES:Volvimos a incluir retrospectivamente a 1201 pacientes diagnosticados con cáncer de recto localmente avanzado y sometidos a quimiorradioterapia neoadyuvante antes de la escisión total del mesorrecto. Eran de cuatro hospitales en China en el período entre enero de 2013 y diciembre de 2020.PRINCIPALES MEDIDAS DE RESULTADO:Los principales resultados fueron la precisión de la predicción de la respuesta patológica completa, medida como el área bajo la curva operativa del receptor para los conjuntos de datos de entrenamiento y validación.RESULTADOS:DeepRP-RC logró un alto rendimiento en la predicción de la respuesta patológica completa después de la quimiorradioterapia neoadyuvante, con valores de área bajo la curva de 0,969 (0,942-0,996), 0,946 (0,915-0,977), 0,943 (0,888-0,998), y 0,919 (0,840-0,997) para los conjuntos de validación interna y las tres externas, respectivamente. DeepRP-RC se desempeñó de manera similar en los subgrupos definidos por la recepción de radioterapia, la ubicación del tumor, los estadios T/N antes y después de la quimiorradioterapia neoadyuvante y la edad. En comparación con los radiólogos experimentados, el modelo mostró un rendimiento sustancialmente mayor en la predicción de la respuesta patológica completa. El modelo también fue muy preciso en la identificación de los pacientes con mala respuesta. Además, el modelo se asoció significativamente con la supervivencia libre de enfermedad independientemente de las variables clinicopatológicas.LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo y la ausencia de datos multiétnicos.CONCLUSIONES:DeepRP-RC podría servir como una herramienta preoperatoria precisa para la predicción de la respuesta patológica completa en el cáncer de recto después de la quimiorradioterapia neoadyuvante. (Traducción-Dr. Felipe Bellolio ).
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Inteligencia Artificial , Quimioradioterapia/efectos adversos , Neoplasias del Recto/terapia , Neoplasias del Recto/tratamiento farmacológico , Imagen por Resonancia Magnética , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: To investigate reliability and changes of in-shoe plantar pressure and shear during walking at three cadences with two insole designs. This was a precursor to the investigation of plantar loading in people with diabetes for potential foot ulcer prevention. METHOD: A sensorised insole system, capable of measuring plantar pressure and shear at the heel, fifth metatarsal head (5MH), first metatarsal head (1MH) and hallux, was tested with ten healthy participants during level walking. Reliability was evaluated, using intra-class correlation coefficient (ICC), while varying the cadences and insole types. Percentage changes in pressure and shear relative to values obtained at self-selected cadence with a flat insole design were investigated. RESULTS: Mean±standard deviation of maximum pressure, medial-lateral and anterior-posterior shear of up to 380±24kPa, 46±2kPa and -71±4kPa, respectively, were measured. The ICC in ranges of 0.762-0.973, 0.758-0.987 and 0.800-0.980 were obtained for pressure, anterior-posterior and medial-lateral shear, respectively. Opposite anterior-posterior shear directions between 5MH and 1MH (stretching), and between 1MH and hallux (pinching) were observed for some participants. Increasing cadence increased pressure and anterior-posterior shear (by up to +77%) but reduced medial-lateral shear at the heel and hallux (by up to -34%). Slower cadence increased anterior-posterior shear (+114%) but decreased medial-lateral shear (-46%) at the hallux. The use of a flexible contoured insole resulted in pressure reduction at the heel and 5MH but an increase in anterior-posterior shear at the heel (+69%) and hallux (+75%). CONCLUSION: The insole system demonstrated good reliability and is comparable to reported pressure-only systems. Pressure measurements were sensitive to changes in cadence and insole designs in ways that were consistent with the literature. However, our plantar shear showed localised shear changes with cadences and insoles for the first time, as well as stretching and pinching effects on plantar tissue. This opens new possibilities to investigate plantar tissue viability, loading characteristics and orthotic designs aimed towards foot ulcer prevention.
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Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/prevención & control , Reproducibilidad de los Resultados , Zapatos , Voluntarios Sanos , CaminataRESUMEN
BACKGROUND: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients. METHODS: LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies, including anticytotoxic T-lymphocyte-associated antigen-4 treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analysed. RESULTS: A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3-71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses and 42.7% (n = 32) partial responses. Four of five cases of LS CRCs displaying proficient MMR (pMMR) or microsatellite stable (MSS) were not responsive. Mucinous/signet-ring cell differentiation was associated with a lower ORR (P = 0.013). The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively. A polyp was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment, and they were all larger than 7 mm. CONCLUSION: PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC. Large LS adenomas may also be eliminated by anti-PD-1 treatment. DATA AVAILABILITY STATEMENT: Due to the privacy of patients, the related data cannot be available for public access but can be obtained from Pei-Rong Ding (dingpr@sysucc.org.cn) upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform (www.researchdata.org.cn).
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Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Humanos , Adulto , Neoplasias Colorrectales Hereditarias sin Poliposis/tratamiento farmacológico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Inhibidores de Puntos de Control Inmunológico , Estudios Retrospectivos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Reparación de la Incompatibilidad de ADN , Inestabilidad de MicrosatélitesRESUMEN
Fluctuations in residuum volume during daily activities are known to occur in lower-limb amputees. This can cause frequent changes to fit, which cannot be accommodated by commonly-used prosthetic sockets. The real-time effects, if any, of these minor socket fit changes on interface biomechanics have not been studied extensively. Amputees commonly use different layers of socks to accommodate frequent volume fluctuations, enabling adjustment of socket fit. We, thus, altered socket fit levels via addition/removal of sock layers to a transtibial amputee who habitually-donned two-sock layers to mimic relatively looser and tighter socket fits. Interface pressure and shear sensors were placed at known prominent load-bearing sites of the transtibial residuum/socket interface, i.e., patellar tendon (PT), popliteal fossa (PF), and anterior-distal (AD) end, to measure real-time biomechanical interactions during standing and level walking. Although socket fit level was only slightly modified, changes in interface pressure and shear across anatomical sites were still observed. Tighter fit corresponds to notable pressure reduction at AD during early stance and pressure increase at PT during terminal stance due to the residuum being pushed up. Shear-to-pressure ratios were used to assess comfort, while pressure- and shear-time integrals were used to assess tissue health. We observed more notable changes at tissue sites (e.g., AD and PF). Combined evaluation of pressure and shear, including shear-to-pressure ratio and time integrals, may offer insight for residuum care.
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Backgrounds: Potato is sensitive to heat stress particularly during plant seedling growth. However, limited studies have characterized the expression pattern of the StGATA family genes under heat stress and lacked validation of its function in potato plants. Methods: Potato plants were cultivated at 30°C and 35°C to induce heat stress responses. qRT-PCR was carried out to characterize the expression pattern of StGATA family genes in potato plants subjected to heat stress. StGATA2 loss-of-function and gain-of-function plants were established. Morphological phenotypes and growth were indicated by plant height and mass. Photosynthesis and transpiration were suggested by stomatal aperture, net photosynthetic rate, transpiration rate, and stomatal conductance. Biochemical and genetic responses were indicated by enzyme activity and mRNA expression of genes encoding CAT, SOD, and POD, and contents of H2O2, MDA, and proline. Results: The expression patterns of StGATA family genes were altered in response to heat stress. StGATA2 protein located in the nucleus. StGATA2 is implicated in regulating plant height and weight of potato plants in response to heat stresses, especially acute heat stress. StGATA2 over-expression promoted photosynthesis while inhibited transpiration under heat stress. StGATA2 overexpression induced biochemical responses of potato plant against heat stress by regulating the contents of H2O2, MDA and proline and the activity of CAT, SOD and POD. StGATA2 overexpression caused genetic responses (CAT, SOD and POD) of potato plant against heat stress. Conclusion: Our data indicated that StGATA2 could enhance the ability of potato plants to resist heat stress-induced damages, which may provide an effective strategy to engineer potato plants for better adaptability to adverse heat stress conditions.
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Background and aims: Mitogen-activated protein kinases (MAPKs) have been reported to respond to various stimuli including heat stress. This research aimed to investigate whether StMAPK1 is implicated in the transduction of the heat stress signal to adapt heat stress as a thermos-tolerant gene. Materials and methods: Potato plants were cultivated under mild (30°C) and acute (35°C) heat stress conditions to analyze mRNA expression of StMAPKs and physiological indicators. StMAPK1 was up-regulated and down-regulated by transfection. Subcellular localization of StMAPK1 protein was observed by fluorescence microscope. The transgenic potato plants were assayed for physiological indexes, photosynthesis, cellular membrane integrity, and heat stress response gene expression. Results: Heat stress altered the expression prolife of StMAPKs. StMAPK1 overexpression changed the physiological characteristics and phenotypes of potato plants under heat stresses. StMAPK1 mediates photosynthesis and maintains membrane integrity of potato plants in response to heat stress. Stress response genes (StP5CS, StCAT, StSOD, and StPOD) in potato plants were altered by StMAPK1 dysregulation. mRNA expression of heat stress genes (StHSP90, StHSP70, StHSP20, and StHSFA3) was affected by StMAPK1. Conclusions: StMAPK1 overexpression increases the heat-tolerant capacity of potato plants at the morphological, physiological, molecular, and genetic levels.
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Pressure coupled with shear stresses are the critical external factors for diabetic foot ulceration assessment and prevention. To date, a wearable system capable of measuring in-shoe multi-directional stresses for out-of-lab analysis has been elusive. The lack of an insole system capable of measuring plantar pressure and shear hinders the development of an effective foot ulcer prevention solution that could be potentially used in a daily living environment. This study reports the development of a first-of-its-kind sensorised insole system and its evaluation in laboratory settings and on human participants, indicating its potential as a wearable technology to be used in real-world applications. Laboratory evaluation revealed that the linearity error and accuracy error of the sensorised insole system were up to 3% and 5%, respectively. When evaluated on a healthy participant, change in footwear resulted in approximately 20%, 75% and 82% change in pressure, medial-lateral and anterior-posterior shear stress, respectively. When evaluated on diabetic participants, no notable difference in peak plantar pressure, as a result of wearing the sensorised insole, was measured. The preliminary results showed that the performance of the sensorised insole system is comparable to previously reported research devices. The system has adequate sensitivity to assist footwear assessment relevant to foot ulcer prevention and is safe to use for people with diabetes. The reported insole system presents the potential to help assess diabetic foot ulceration risk in a daily living environment underpinned by wearable pressure and shear sensing technologies.
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Diabetes Mellitus , Pie Diabético , Ortesis del Pié , Dispositivos Electrónicos Vestibles , Humanos , Pie Diabético/diagnóstico , Pie Diabético/prevención & control , Pie , Zapatos , PresiónRESUMEN
We report the systematic development of an electrooxidative methodology that translates stoichiometric C-H fluorination reactivity of an isolable CuIII fluoride complex into a catalytic process. The critical challenges of electrocatalysis with a highly reactive CuIII species were addressed by the judicious selection of electrolyte, F- source, and sacrificial electron acceptor. Catalyst-controlled C-H fluorination occurs with a preference for hydridic C-H bonds with high bond dissociation energies over weaker but less hydridic C-H bonds. The selectivity is driven by an oxidative asynchronous proton-coupled elelctron transfer (PCET) at an electrophilic CuIII-F complex. We further demonstrate that the asynchronicity factor of hydrogen atom transfer η can be used as a guideline to rationalize the selectivity of C-H fluorination.
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BACKGROUND: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti-PD-1 treatment for localized mismatch repair-deficient (dMMR) colorectal cancer (CRC). PATIENTS AND METHODS: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors. RESULTS: A total of 73 patients were included. Most of the tumors were locally advanced, including 19 (26.0%) T4a and 29 (39.7%) T4b. Most patients (79.5%) received PD-1 inhibitor monotherapy. Objective response per radiologic assessment was achieved in 62 (84.9%) patients, including 17 (23.3%) with complete response (CR) and 45 (61.6%) with partial response, with a median time to response of 9.6 weeks. Patients with T4a/4b disease had a similar response rate as those with T2-3 disease (84.0% vs 85.4%; P=.999). As of writing, a total of 50 patients have undergone surgery. Pathologic CR was achieved in most (57.1%) patients and remained high (59.5%) even among the 38 patients with T4a/4b disease. The 17 patients with CR did not undergo surgery and adopted a watch-and-wait strategy. After a median follow-up of 17.2 months (range, 3.4-45.1 months), the overall median recurrence-free and overall survivals were not reached. Among patients undergoing surgery or achieving CR, the 2-year tumor-specific disease-free and overall survival rates were both 100%. During neoadjuvant treatment, grade 3-4 adverse events occurred in 8 patients; 4 required acute intervention. Severe postoperative complications were recorded in 4 patients, 3 of whom required a second surgery. CONCLUSIONS: Neoadjuvant therapy with PD-1 blockade is highly effective for localized dMMR CRC, with an acceptable safety profile and low recurrence rate. This treatment holds promise for becoming the new standard of care for localized dMMR CRCs.